It has been recently reported from this lab that opioid receptors exist in myocardial membranes, and that opioid agonists have negative inotropic effects in the heart. In intact animals and in the isolated heart, opioid agonists inhibit NE release from neuron endings. However, whether stimulation of myocardial opioid (OP) receptors modifies the response to beta-adrenergic receptor (BAR) stimulation at postsynaptic levels is unknown. Our studies in individual rat ventricular myocytes (electrically stimulated at 0.5 Hz at 23 degrees C) demonstrate that the increase in cytosolic Ca 2+ transient (indexed by indo-1 fluorescence) and contraction (measured via photodiode array amplitudes and increase in the sarcolemmal L type Ca 2+ current I Ca) in response to norepinephrine (NE, 10 -7M) are abolished by the addition of 10 -8M Leucine enkephalin (LE), a delta OP agonist. The LE effect was reversed by Naloxone (Nal, 10 -8M). Thus, stimulation of the delta OP receptors on heart cells can "short circuit" the BAR mediated response and may protect against cell Ca 2+ overload during stress.